Compositions for dental prophylaxis

ABSTRACT

COMPOSITIONS FOR REMOVING SOFT TARTAR AND OTHER CALCIUM DEPOSITS FORM TEETH COMPRISING A TOOTH PASTE OR TOOTH POWDER AND A MONOCALCIUM MONOMAGNESIUM POLY LOWER ALKANOL AMINO ETHYLENE DIAMINE TETRA ACETATE: GLUCONO CITRATE COMPLEX AS SEQUESTERING AND CHELATING AGENT.

United States Patent 3,558,769 COMPDSITIONS FOR DENTAL PROPHYLAXISAlfred R. Globus, Long island City, N.Y., assignor to Guardian ChemicalCorporation, Long Island City, N.Y., a corporation of Delaware NoDrawing. Original application Sept. 24, 1965, Ser. No. 490,128, nowPatent No. 3,452,049. Divided and this application Dec. 30, 1968, Ser.No. 801,890

Int. Cl. A61k 7/16 US. Cl. 424-54 10 Claims ABSTRACT OF THE DISCLOSURECompositions for removing soft tartar and other calcium deposits fromteeth comprising a tooth paste or tooth powder and a monocalciummonomagnesium poly lower alkanol amino ethylene diamine tetra acetate:glucono citrate complex as sequestering and chelating agent.

This application is a division of Ser. No. 490,128, filed Sept. 24,1965, now Pat. No. 3,452,049.

This invention relates to chelating and sequestering agents. It moreparticularly relates to a particular chelating and sequestering agentfor use in sequestering calcium. This invention has particular utilityin removing soft tartar and other calcium deposits from teeth.

While there have been many attempts made to remove, using chemicalmeans, the thin films and superficial stains caused by calciumdeposition from the teeth and to prevent the formation of tartar whichis a calcareous deposit on the tooth enamel, these have not provedsuccessful, for such means as have been successful in removing orpreventing such deposits, inevitably etched or opaqued the teeth.

The sequestering and/or chelating agents which have been effective inremoving these deposits, when used in sufiiciently high concentrationshave also resulted in extensive tooth damage. This has been demonstratedconclusively on extracted teeth, the destruction effect of such agentsbecoming immediately apparent.

This invention has for an object the production of a novel chelating andsequestering agent.

Another object of this invention is to provide a method of manufacturingthe novel chelating and sequestering agent of this invention.

Still another object of the invention is to provide a novel chelatingand sequestering agent capable of removing soft tartar and other calciumdeposits from teeth Without any untoward side effects.

A further object of this invention is to provide a novel prophylacticcomposition utilizing the chelating and sequestering agent of thisinvention.

Other and additional objects of this invention will become apparent froma consideration of this entire specification.

The novel sequestering and chelating agent of this invention is suitablyprepared by mixing citric acid, D- gluconic acid and mildly alkalinemagnesium hydroxy carbonate and heating the mixture to an extent andtemperature sufficient to remove water but below the decompositiontemperature of any component of the mixture or of the dehydrationproduct thereof. The magnesium glucono citrate thus formed is reactedwith ethylene diamine, tetra-acetic acid in an aqueous alkanol aminesolution, such as, for example, propanol amine, tri-ethanol amine,mono-ethanol amine, etc. The product thus formed is a magnesiumpolyamino ethylene diamine tetra-acetate; glucono citrate complex.

The magnesium hydroxy carbonate used in-the preparation of this compoundis somewhat special. Since mild ice alkalinity of the magnesiumcontaining moiety is essential, it is not possible to use magnesiumoxide or hydroxide since they are too alkaline. Similarly, magnesiumcar-' bonate cannot be used because it is not sufiiciently alkaline forthe purposes of this synthesis. An addition product, however, ofmagnesium oxide to slurried magnesium carbonate produces an excellent,mildly alkaline magnesium hydroxy carbonate which is well suited to thepractice of this invention. The addition product is dried and thenground to a proper state of fineness for use in reaction with a citricacid and gluconic acid, as set forth above. An alternate of theaforementioned preparation of magnesium hydroxy carbonate involves theslurrying of magnesium hydroxide, carbonation of the slurry, drying ofthe carbonate slurry, and grinding as aforesaid.

The mono-magnesium polyamino ethylene-diamine tetraacetate:gluconocitrate complex capable of binding calcium is then reacted with acalcium salt and preferably calcium phosphate, e.g., calcium hydrogenphosphate or calcium ortho-phosphate whereby a magnesium calciumpolyamino ethylene-diamine tetra-acetatezglucono citrate complex isformed. Each mol of the complex in accordance with the invention canhold two bivalent cations, e.g., a di-rnagnesium, mono-magnesiummono-calcium or di-calcium complex is possible. As there is formed asthe intermediate a mono-magnesium complex, the intermediate product iscapable of binding one more bivalent cation. On reaction with thecalcium salt there is formed accordingly a mono-calcium compound whichcan bind one more bivalent cation. This compound is the chelating andsequestering agent of this invention. The mono-magnesium mono-calciumcomplex acts rapidly to withdraw calcium from the tartar and other softdeposits on the tooth causing absolutely no etching of the tooth enamel.This is because the mono-magnesium mono-calcium complex only removescalcium in the form of soft tartar but not calcium which is a componentof the tooth enamel.

The preparation of the magnesium hydroxycarbonate is hereinafter setfourth in detail, although it is to be understood that other methods ofproducing the same may be employed.

A heavy slurry of magnesium carbonate with magnesium hydroxide isprepared having a ratio of not less than 2 /2 mols of magnesiumcarbonate to each mol of magnesium hydroxide and preferably having aratio of 4 mols of magnesium carbonate to 1 mol of magnesium hydroxide.The slurried material is first dried under vacuum or, alternatively,dried at low temperatures in order to remove the water, and the driedproduct heated to a temperature of at least C. and preferably to atemperature of between -l75 C. but not higher than 220 C. as the samemay result in inactivation. During the drying, the weight loss of theresulting magnesium hydroxycarbonate as compared with the previouslythoroughly dried product used as starting material is from 35-39%.

The heating is most advantageously carried out slowly in order to avoiddecomposition by undue calcination with a resultant decrease inactivity. Generally, the temperature of the dried powder is raisedslowly over a period,

of 4-6 hours to the final temperature and maintained at that temperaturefor another 8-16 hours in order to attain equilibrium. The resultingwhite to slightly yellowish powdery product is ground and screened assome lumping may have taken place.

The ground material is added to the starting mixture of citric acid andgluconic acid which has first been dried under vacuum at 60-70 C. If thestarting citric acid is designated as anhydrous no preliminary dryingmay be necessary.

The dried magnesium hydroxycarbonate is employed in an amount of from15-48 parts by weight, and preferably from -40 parts by weight per 100parts by weight of the dry acids.

After intimate mixing and grinding, if the same is necessary, themixture is subjected to slow and gradual heating to a temperature abovethe boiling point of water, genarally to about 120 C. and mostpreferably between 1l0125 C. and the heating continued for a period of15-24 hours. Temperatures of 130 C. must be avoided as the use ofexcessively high temperatures will cause fusing of the product into asolid cake.

The time required for the heating may be reduced somewhat by treatingthe product in the form of thin layers and also by sweeping out theatmosphere in the heating oven by means of an inert gas, such as, forexample, nitrogen or argon. The use of carbon dioxide must be avoided asthe same is not inert in the instant process and under no circumstancescan be employed.

During the heating, the mixture of previously thoroughly dried powdersagain splits ofi. water, approximately 3.6-4.2% by weight of the charge,and then attains equilibrium. Further heating at these temperaturesproduces very little weight change. The water which is split off appearsto be derived from the original acids and not by reaction of the acidswith the magnesium hydroxycarbonate, the latter remaining substantiallyunchanged as is evidenced by the fact that very little carbon dioxide isreleased during the heating steps as would have been the case if anappreciable reaction had taken place between the acids and the magnesiumhydroxycarbonate.

In accordance with the invention, the ethylene-diamine tetra-acetic acidi suspended in water and the magnesium glucono citrate is added whilerapidly stirring the mix ture, reaction taking place to form magnesiumethylenediamine tetra-acetic acidzglucono citrate. The alkanolamine isadded slowly during the reaction, the pH being adjusted upwardly untilthe suspension clears. Preferably during this time the mixture is heatedup to 7090 C. for several hours to react the alkanolamine gluconocitrate and ethylene-dia mino tetra-acetic acid to form a solution ofabout 46% of complex. Heating is not necessary as the reaction willproceed albeit slowly at room temperature. As alkanolamine,ethanolamine, diethanolamine, triethanolamine, propanolamine,hexanolamine may be employed. An excess of the alkanolamine, i.e.,ethanolamine, is then added after solution has been achieved to providea stable complex. If the complex is formed in the absence of heat, thereaction solution must be allowed to stand for several days. Where heatis employed, several hours are sufiicient to complete formation of thecomplex. Stability of the complex is obtained by bringing the solutionup to a pH of about 8 by addition to the solution of an excess of thealkanolamine.

The product magnesium polyalkanol-amino ethylenediamine tetra acetate:glucono citrate complex is then reacted with an equivalent amount of aninsoluble calcium phosphate [CaHPO or Ca(PO at 48 C. for 4 hours tointroduce calcium to produce mono-magnesium monocalcium polyalkanolaminoethylenediamine tetra acetate: glucono citrate.

The sequestering and chelating agent of this invention is used inconventional toothpaste or tooth powder formulation such as thefollowing:

TOOTHPASTE Parts by weight Carboxymethyl cellulose 1 70% sorbitol 29.8

Water 8 Soluble saccharin .1 Hyamine 10X .1 Dicalcium phosphate Duohydrate Diatomaceous earth (finest polished grade) 27 Mineral oil 80-90viscosity 1 Sodium lauryl sulfate 2 Peppermint oil 0.5 Spearmint oil 0.5

TOOTH POWDER Parts by weight Carboxymethyl cellulose 1 Soluble saccharin.1 Hyamine 10X .1 Dicalcium phosphate Duo hydrate 30 Diatomaceous earth(finest polished grade) 40.8 Sodium lauryl sulfate 2 Peppermint oil .5Spearmint oil .5 Air-floated silica i 25 The complex is suitable for useas a 40 or 50 weight percent solution. If available, it can be used inthe dry state. The chelating and sequestering agent of this inventionhas a pH of about 7 to 8.5 preferably 7.8 to 8.2. It has beenestablished in testing to be non-toxic to rats in doses of up to 5 gramsper kilo and has in simulated long-use testing been shown to benon-eroding and non-etching with respect to the enamel of the teeth.

The magnesium polyamino ethylene diamine tetra-acetate:glucono citratecomplex, in accordance with the invention, can be converted into itsmono-calcium derivative in accordance with another feature of thisinvention by introducing the magnesium polyamino ethylene-diaminetetra-acetatezglucono citrate complex to a toothpaste or powderformulation containing calcium. In order not to form the dicalciumderivative, all of the calcium present in the toothpaste or tooth powderformulation must be in insoluble form, preferably in the form of acarbonate, phosphate or silicate. Preferably, the calcium is introducedinto the formulation as dicalcium phosphate. The dicalcium phosphate hasbeen found under no circumstances to result in the formation of thedicalcium complex derivative. If a small excess of calcium is present inthe insoluble form, only the mono-calcium derivative is obtained.Preferably, the mono-calcium derivative is formed in an alkaline mediumand, most preferably, at a pH of 8 to 8.5. In an acid medium, hydrolysisof the magnesium polyamino-ethylene diamine tetra acetate: gluconocitrate complex takes place.

In forming the toothpaste or tooth powder formulation capable ofremoving plaque from teeth and retarding or preventing tartar formationwithout etching or damaging the dental enamel in any way, the complex inaccordance with the invention is employed in a concentration of 1 to25%, and preferably in a concentration of within the range of 5 to 10%.

The following examples are illustrative of the invention but are not tobe construed as limiting thereof:

EXAMPLE 1 A slurry of 3.5 moles of magnesium carbonate and 1 mol ofmagnesium hydroxide was prepared. The slurried material was dried inorder to remove the water and the dried product heated to 115 C. for 16hours. The resulting powder was ground and added to a mixture of a11-hydrous citric and gluconic acids. The dried magnesium hydroxycarbonatewas employed in an amount of 45 parts by weight per parts by weight ofthe dry acid. The mixture was subjected to heating at a temperature ofC. for 16 hours. The product was off-white to yellowish in color and hadthe following composition:

Percent Free citric acid (anhydrous) and D-gluconic lactones 59Magnesium salts of said acids 6 Magnesium hydroxycarbonate 32 Citraconicacid 0.2 Balance Inert materials EXAMPLE 2 Example 1 was repeated exceptthat the mixture of acids was replaced with an equal amount of a mixtureof gluconic and citric acid in its hydrated form. Theresulting producthad the following composition:

Percent Free citric acid (anhydrous) and D-gluconic lactones 53.7Magnesium salts of said acids l 7.0 Magnesium hydroxycarbonate 33.5Balance Inert materials EXAMPLE 3 Example 1 was again repeated exceptthat 53 parts of citric acid, 7 parts of gluconic acid, 26 parts ofmagnesium hydroxycarbonate, and 4 parts of magnesium acid citrate wereused. The resulting product had the following composition:

Percent Free citric acid (anhydrous) and D-gluconic lactones 57.3Magnesium salts of said acids 5.0 Magnesium hydroxycarbonate 24.0Balance Inert materials EXAMPLE 4 2.5 grams of magnesium glucono:citratemixed with 22 grams of ethylenediamine tetra-acetic acid dissolved intriethanolamine and heated for 4 hours at 70 C. to produce 46 grams ofmagnesium triethanolamine ethylenediamine tetra-acetatezglucono citrate.

EXAMPLE 5 Example 4 was repeated using in place of triethanolamine,diethanolamine to produce 41 grams of magnesium diethanolamine ethylenediamine tetra-acetatezglucono citrate.

EXAMPLE 6 46 grams of the product of Example 4 were admixed with 50grams of calcium orthophosphate and the mixture heated for 2 hours at 80C. to produce the mono-calcium mono-magnesium triethanolamineethylene-diarnine tetraacetate: glucono citrate complex.

EXAMPLE 7 A toothpaste formulation in accordance with the invention wasprepared having the following composition:

EXAMPLE 8 A tooth powder formulation in accordance with the inventionwas prepared having the following composition:

Parts by weight Carboxy methyl cellulose 1 Soluble saccharin .1 Hyamine10X .1 Dicalcium phosphate Duo hydrate 30 Diatomaceous earth (finestpolished grade) 40.8 Sodium lauryl sulfate 2 Peppermint oil .5 Spearmintoil .5 Air-floated silica 25 Magnesium polymonoethylene diamine tetraacetate: glucono citrate complex 7 I claim: 1. A composition for dentalprophylaxis comprising:

Parts by weight Carboxymethyl cellulose 1 70% sorbitol 22.8 Water 8Soluble saccharin .l Hyamine 10X .1 Dicalcium phosphate Duo hydrate 30Diatomaceous earth (finest polished grade) 27 Mineral oil -90 viscosity1 Sodium lauryl sulfate 2 Peppermint oil 0.5 Spearmint oil 0.5 A memberselected from the group consisting of magnesium mono-lower alkanol aminoethylenediamine tetra-acetatezglucono citrate complex, magnesiumdi-lower alkanol amino ethylene-diamine tetra acetatezglucono citratecomplex and magnesium tri-lower alkanol amino ethylene-diaminetetra-acetatezglucono citrate 7 2. The method of removing soft tartar orcalcium-containing deposits from teeth, which comprises contacting suchteeth with the composition described in claim 1.

3. A composition for dental prophylaxis comprising:

Parts by weight 4. The method of removing soft tartar orcalcium-containing deposits from teeth, which comprises contacting suchteeth with the composition described in claim 3.

5. The method of removing soft tartar or calcium-containing depositsfrom teeth which comprises contacting such teeth with a 'member selectedfrom the group consisting of monocalcium monomagnesium mono-lower a1-kanol amino ethylene-diamine tetra-acetate:gluconocitrate, monocalciummonomagnesium di-lower alkanol amino ethylene-diaminetetra-acetate:gluconocitrate and monocalcium monomagnesium tri-loweralkanol amino ethylene diamine tetra-acetatezglucono citrate.

6. A composition for dental prophylaxis which comprises a toothpasteconsisting of the following:

' Parts by weight Carboxymethyl cellulose 1 70% sorbitol 29.8 Water 8Soluble saccharin .1 Hyamine 10X .1 Dicalcium phosphate Duo hydrate 30Diatomaceous earth (finest polished grade) 27 Mineral oil 80-90viscosity 1 Sodium lauryl sulfate 2 Peppermint oil 0.5 Spearmint oil 0.5

A member selected from the group consisting of magnesium mono-loweralkanol amino ethylene- 7 diamine tetra-acetate:gluc0no citrate complex,magnesium di-lower alkanol amino ethylene-diamine tetra-acetate:gluconocitrate complex and ethylene-diamine tetra-acetatezglucono citrate 1-257. A composition according to claim 6 wherein said mono calcium monomagnesium lower alkanol amino ethylene diamine tetra acetate: gluconocitrate is present in an amount of from 5 to 10%.

8. A composition for dental prophylaxis, which comprises a toothpowderconsisting of the following:

Parts by weight A member selected from the group consisting of magnesiummono-lower alkanol amino ethylenediamine tetra-acetate2glucono citratecomplex, magnesium di-lower alkanol amino ethylene-diaminetetra-acetate:glucono citrate 1-25 9. A composition for dentalprophylaxis according to claim 8 where said mono calcium monomagnesiumlower alkanol amino ethylene diamine tetra acetatezglucono citrate ispresent in an amount of from 5 to 10%.

10. A composition for dental prophylaxis comprising a toothpaste orpowder formulation containing a member selected from the groupconsisting of monocalcium monomagnesium mono-lower alokanl aminoethylene-diamine tetra-acetatezglucono citrate, monocalcium monomagnesium di-lower alkanol amino ethylene-diaminetetraacetatezgluconocitrate and monocalcium monomagnesium tri-loweralkanol aminoethylene diamine tetra-acetate: gluconocitrate wherein saidalkanol moiety contains up to 6 carbon atoms.

References Cited Grossrnan, J. Oral Surg., Oral Med., and Oral Path.,vol. 7, pages 484-487, May 1954.

RICHARD L. HUFF, Primary Examiner

